First FDA-approved study of cannabis for PTSD in veterans underway

NEW YORK — In a symposium on the issues and controversies surrounding marijuana, internist and telemedicine physician Sue Sisley, MD, discussed the design and aim of her FDA-approved phase 2 study of cannabis for PTSD in U.S. military veterans.

Sisley, who was terminated from the University of Arizona after becoming the principle investigator on the cannabis study, said she was anti-cannabis for many years of her life, though the veterans she was treating touted the drug’s benefits on various symptoms they experienced.

“I was dismissive and judgmental, then I started losing a lot of vets in my practice to suicide, and it became a big wake-up call,” she said. “... The veteran community has a higher rate of prescription drug overdose, and many vets discovered they can substitute cannabis for the more addictive medications they’ve been prescribed, which is how we started to examine this."

The study, which is funded by a $2.15 million grant from University of Colorado, is the first controlled clinical trial in the world to evaluate smoked medical cannabis as treatment for PTSD.

After what Sisley described as a 7-year struggle with the government, she finally received the “golden ticket” to begin her research.

The phase 2, triple-blind, outpatient, randomized, placebo-controlled study includes 60 veterans who were randomly assigned to one of four arms: high THC (12%), high CBD (12%), 1:1 ratio of THC to CBD (8%/8%), or placebo.

In a familiarization stage, participants undergo two 4-hour self-administration sessions. Sisley and colleagues are present during administration to ensure cannabis is well-tolerated and that vitals and side effects are documented.

Following the familiarization phase, participants are invited to take cannabis home and self-administer for 3 weeks at doses they see appropriate, with the goal of targeting PTSD symptoms, then stopping. Any unused cannabis is returned to Sisley, who then weighs the excess to gain an understanding of the day-to-day amounts required. Though participants receive up to 2 g per day (the equivalent of two rolled cigarettes), Sisley said surprisingly very few need that much to manage their symptoms.

After 3 weeks of self-administration, participants remain abstinent for 2 weeks, during which time Sisley and colleagues monitor to ensure their PTSD symptoms have not relapsed and that they are not experiencing drug withdrawal. Participants then enter the stage-2 crossover phase where they are randomized to a different dose for 3 weeks, followed by 2 weeks of abstinence.

The primary endpoint is Clinician-Administered PTSD Scale (CAPS) score administered after 3 weeks of self-administration. Secondary endpoints include PTSD symptom checklist based on DSM-5, actigraphy (objective sleep measure); Inventory of Depression and Anxiety Symptoms (IDAS); Timeline Follow-Back (TLFB); and Inventory of Psychosocial Functioning (IPF).

The study will also assess biomarkers for inflammation, including IL-6 and IL-17. According to Sisley, anti-inflammatory action of cannabis is a big area of research focus.

The trial is currently in its third year and enrollment is ongoing. Sisley and colleagues need 19 additional veterans to complete the dataset. She is hopeful that if the data are compelling, the FDA will approve a phase-3 trial.

Unfortunately, she has concerns regarding the potency of the cannabis supplied by the government, which contains extraneous plant material like sticks and seeds. “If half is extraneous nonmedical plant material, it could be sabotaging efficacy studies, meaning that if you’re trying to measure effectiveness of cannabis and you’re forced to use a very sub-optimal plant material, this could harm the outcome of tests looking at how effective cannabis is at treating a certain illness,” she said. – by Stacey L. Adams

Reference:

Sisley SA. Issues and controversies around marijuana use: What’s the buzz?. Presented at: American Psychiatric Association Annual Meeting; May 5-9, 20178; New York.

Disclosures: Sisley reports no relevant financial disclosures.